The Respiratory Epithelium. IV. Histogenesis of Epidermoid Metaplasia and Carcinoma In Situ in the Hamster23

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Abstract
The histogenesis of epidermoid metaplasia and carcinoma in situ was studied in female hamster tracheobronchial epithelium during and after 15 weekly intratracheal instillations of a benzo[a]pyrene-ferric oxide (BP-Fe2O3) mixture in saline. Within 24 hours after the first instillation of BP-Fe2O3, goblet cell hyperplasia had occurred. Mitoses were observed in small mucous granule cells (SMGC). SMGC probably represent mature mucous cells at early stages of their secretory cycle. Ciliated cells were extruded, and by 1 week after the first instillation the epithelium was repopulated with mucous cells. During 1–5 weeks the mucosubstances in these cells became more acidic, and the epithelium was composed of more than one cuboidal mucous cell layer. At 1 week after the fifth carcinogen instillation, the epithelium was composed of basal cells and metaplastic cuboidal and flattened surface mucous cells (epidermoid metaplasia). Extensive keratinization occurred at 10 weeks (cornifying epidermoid metaplasia). The luminal cornifying epidermoid cells contained periodic acid-Schifff-positive, diastase-resistant mucosubstances. Localized areas of marked atypical metaplasia and carcinoma in situ were observed 20–50 weeks after the first instillation. They were characterized by one to two layers of basal cells and five to ten layers of pleomorphic cuboidal cells. The surface cells had all the characteristics of mucous cells, and cells near the basal lamina showed features of epidermoid cells. Mucus-filled intraepithelial cysts were observed. These data support the hypothesis of conversion of mucous cells to metaplastic and neoplastic cells.